Intestinal Tuberculosis Patients Research Articles

High Adenosine Deaminase Level and Erythrocyte Sedimentation Rate of Intestinal Tuberculosis Patients

BACKGROUND: Currently, laboratory diagnosis of intestinal tuberculosis (ITB) is limited based on clinical manifestations, providing opportunities for alternative laboratory tests to diagnose ITB. At the present time, the role of serum adenosine deaminase (ADA) and hematological tests in ITB patients are not widely known. The objective of this study was to determine the role of ADA and hematological tests in patients suspected with ITB.METHODS: Subjects that were suspected of ITB were classified as ITB group, while subjects with inflammatory bowel disease, hemorrhoid, and intestinal malignancy were classified as non-ITB group. Colonoscopy, histopathological examinations, and hematological test were performed. ADA measurement was also performed with clinical chemistry analyzer based on enzymatic colorimetry principle.RESULTS: Out of 143 subjects, 16 (11.2%) subjects were diagnosed with ITB and 127 (88.8%) subjects were classified as non-ITB group. ADA level and erythrocyte sedimentation rate (ESR) of ITB group were significantly higher than the ones of non-ITB group (p<0.05). Cut-off, sensitivity, and specificity of ADA level were 12.56 IU/L, 75%, and 57%, respectively. Cut-off, sensitivity, and specificity of ESR were 32.5 mm/hour, 81%, and 62%, respectively. Colonoscopy of ITB subjects displayed multiple ulcerations, edema, and hyperemic mucosa. Histopathological examination of ITB subjects exhibited granulomatous inflammation, epitheloid cells, giant cells, and lymphocyte aggregates.CONCLUSION: ADA level and ESR were significantly higher among ITB patients compared with non-ITB patients. Since the sensitivities of ADA and ESR tests were high, the ADA and ESR tests could be considered as a screening test for ITB.KEYWORDS: intestinal tuberculosis, adenosine deaminase, hematological tests

The gut microbiome: A line of defense against tuberculosis development.

The tuberculosis (TB) burden remains a significant global public health concern, especially in less developed countries. While pulmonary tuberculosis (PTB) is the most common form of the disease, extrapulmonary tuberculosis, particularly intestinal TB (ITB), which is mostly secondary to PTB, is also a significant issue. With the development of sequencing technologies, recent studies have investigated the potential role of the gut microbiome in TB development. In this review, we summarized studies investigating the gut microbiome in both PTB and ITB patients (secondary to PTB) compared with healthy controls. Both PTB and ITB patients show reduced gut microbiome diversity characterized by reduced Firmicutes and elevated opportunistic pathogens colonization; Bacteroides and Prevotella were reported with opposite alteration in PTB and ITB patients. The alteration reported in TB patients may lead to a disequilibrium in metabolites such as short-chain fatty acid (SCFA) production, which may recast the lung microbiome and immunity via the "gut-lung axis". These findings may also shed light on the colonization of Mycobacterium tuberculosis in the gastrointestinal tract and the development of ITB in PTB patients. The findings highlight the crucial role of the gut microbiome in TB, particularly in ITB development, and suggest that probiotics and postbiotics might be useful supplements in shaping a balanced gut microbiome during TB treatment.

Interferon-gamma release assay has poor diagnostic accuracy in differentiating intestinal tuberculosis from Crohn's disease in tuberculosis endemic areas.

Intestinal tuberculosis (ITB) and Crohn's disease (CD) frequently present with a diagnostic dilemma because of similar presentation. Interferon-gamma release assay (IGRA) has been used in differentiating ITB from CD, but with sparse reports on its diagnostic accuracy in tuberculosis endemic regions and this study evaluated the same. Patients with definitive diagnosis of ITB (n=59) or CD (n=49) who underwent IGRA testing (n=307) were retrospectively included at All India Institute of Medical Sciences, New Delhi (July 2014 to September 2021). CD or ITB was diagnosed as per standard criteria. IGRA was considered positive at >0.35 IU/mL. Relevant data was collected and IGRA results were compared between ITB and CD to determine its accuracy. Among 59 ITB patients (mean age, 32.6±13.1 years; median disease duration, 1 year; male, 59.3%), 24 were positive and 35 tested negative for IGRA. Among 49 CD patients (mean age, 37.8±14.0; median disease duration, 4 years; male, 61.2%), 12 were positive and 37 tested negative for IGRA. Hence, for diagnosing ITB, IGRA showed a sensitivity, specificity, positive and negative predictive values of 40.68%, 75.51%, 66.67%, and 51.39%, respectively. The area under the curve of IGRA for ITB diagnosis was 0.66 (95% confidence interval, 0.55-0.75). In a subset (n=64), tuberculin skin test (TST) showed sensitivity, specificity, positive and negative predictive values of 64.7%, 73.3%, 73.3%, and 64.71%, respectively. IGRA and TST were concordant in 38 (59.4%) patients with κ=0.17. In a tuberculosis endemic region, IGRA had poor diagnostic accuracy for differentiating ITB from CD, suggesting a limited value of IGRA in this setting.

Genome-wide DNA methylation profiling in differentiating Crohn's disease from intestinal tuberculosis.

Differential diagnosis of Crohn's disease (CD) and intestinal tuberculosis (ITB) is still difficult in clinical pratice. DNA methylation has been considered as a favorable area for biomarker exploration and identification. The purpose of the current study was to evaluate DNA methylation changes between CD and ITB. We performed a genome-wide association study to identify differentially methylated positions (DMPs), including 8 CD patients (before the initial of biologics or immunomodulators), 6 ITB patients, and 8 healthy controls (HCs), in whole blood DNA using the Infinium HumanMethylation850 BeadChip. Patients in the CD group and ITB group were all observed with hypo-methylated changes compared with HCs. However, the CD group overlaps with the ITB group in DNA methylation, suggesting a stable epigenetic profile between the two diseases. The pathway enrichment analysis showed the alternation in inflammation-related pathway, immune system, and signal transduction. Focused on the DMPs located in the promoter region, further analysis indicated hypermethylation of cg03122532 (5'UTR of KCNJ15) could be a potential CD-specific biomarker. We identified specific differential methylation loci related to CD and ITB in blood DNA. DNA metylation as a important epigenetic modification could contribute to the pathogenesis study and biomarker exploration of the diseases.

Enterogenous Microbiotic Markers in the Differential Diagnosis of Crohn's Disease and Intestinal Tuberculosis.

Crohn’s disease (CD) is a chronic intestinal disorder characterized by refractory gastrointestinal ulcerations. Intestinal tuberculosis (ITB) is one common intestinal disease in east Asia. The two diseases share similar clinical manifestations and endoscopic characteristics. Thus, it is difficult to establish a definite diagnosis of CD, CD concomitant with ITB (CD-ITB), and ITB in practice. Some enterogeneous microbiotic markers have been applied to differentiate CD and ITB, but it remains unknown how they work for the three groups of patients. The aim of our study was to explore the diagnostic values of these enterogeneous microbiotic markers (ASCA IgG, ASCA IgA, ACCA, Anti-I2 and AMCA) among CD, CD-ITB, and ITB patients. A total of 124 individuals were retrospectively enrolled in this study, namely, 103 CD patients, 10 CD-ITB patients, 9 ITB patients, and 68 healthy controls. The demographic and clinical characteristics of these patients were collected and analyzed. The values of these individual or combined enterogeneous microbiotic markers in diagnosis and classification were assessed in CD, CD-ITB, and ITB patients. ASCA IgG, ASCA IgA, and AMCA could accurately differentiate CD patients from healthy controls with an area under curve (AUC) of 0.688, 0.601, and 0.638, respectively. ASCA IgG was significantly higher in CD patients than in CD-ITB patients (P = 0.0003). The Anti-I2 antibody was appropriate for distinguishing CD-ITB from ITB patients (P = 0.039). In CD patients, ASCA IgG was higher in severe patients than in mild (P <0.0001) and inactive patients (P <0.0001), respectively. AMCA was significantly elevated in severe and moderate patients compared to inactive patients (P = 0.001, P = 0.003, respectively). AMCA was associated with a higher risk of CD-related surgery with a significant P-value of 0.0038. In our cohort, ASCAs and AMCA could accurately distinguish CD from healthy controls with an acceptable AUC. A combination of elevated ASCA IgG and AMCA antibodies established a higher sensitivity in differentiating CD from healthy controls. Elevated ASCA IgG demonstrated a differential diagnostic value between CD and CD-ITB. Anti-I2 could also distinguish CD-ITB from ITB. The level of AMCA was associated with both disease severity and CD-related surgery. Likewise, the level of ASCA IgG was also related to disease severity.

Differentiating Crohn’s disease from intestinal tuberculosis using a fusion correlation neural network

Crohn’s disease (CD) and intestinal tuberculosis (ITB) have many similarities and overlaps in their clinical manifestations and medical imaging features, which makes it difficult to accurately differentiate CD from ITB. Random forests have unique advantages in discovering specific indicators and measuring relevance. By fusing the attributes and the correlation information between the sample and training set, we propose a fusion correlation neural network (FCNN) to diagnose CD and ITB patients. A total of 287 cases with fifty-nine indicators were collected from the Second Xiangya Hospital of Central South University. An FCNN allows one to explain the feature selection and learning classification rules in neural networks. The experiments show that perianal fistulas, skin and mucosal lesions, intestinal perforation, comb sign, and cobblestone appearance tend to be associated with CD; and ascites show a higher association with intestinal tuberculosis. These conclusions are consistent with the experience of clinicians. Finally, the age, disease course, white blood cell, hemoglobin, platelets, C-reactive protein, and T-SPOT of patients were used to train the FCNN. The average accuracy of the FCNN exceeds 91%, showing better performance than existing linear regression standards and other machine learning models.

Socio-demographic Characteristics of Surgically Resected Histopathological Confirmed Intestinal Tuberculosis Patients attended at a Tertiary Care Hospital in Dhaka City

Background: Intestinal tuberculosis can occur in different socio-demographic characteristics.&#x0D; Objective: The purpose of the present study was to see socio-demographic characteristics of surgically resected histopathological confirmed intestinal tuberculosis patients.&#x0D; Methodology: This cross-sectional study was conducted at the Department of surgery, Dhaka Medical College hospital, Dhaka from July 2005 to December 2007 for a period of two and a half year. Purposive sampling was followed as per inclusion and exclusion criteria. The patients were evaluated based on history, physical examination, laboratory investigations and other relevant investigations.&#x0D; Result: Total numbers of cases in this series were 50 cases. The youngest patient of the series was 15 years and the oldest was 60 years. The average age of the patients was 34.5±12.6 years. Out of 50 patients 64.0% cases were male and 36.0% cases are female with a male to female ratio 1.77:1. Most of the patients were farmer which was 52.0% cases. In this study 37(74.0%) cases came from lower socio-economic condition. Majority cases were in poor nutritional status (84.0%) and came from rural area (56.0%). In this study 40.0% patients were vaccinated and 50.0% cases were smoker.&#x0D; Conclusion: In conclusion adult middle age male farmers with low-socioeconomic condition patients are most commonly suffering from intestinal tuberculosis.&#x0D; Bangladesh Journal of Infectious Diseases June 2021;8(1):7-11

Gut Microbiome in Probable Intestinal Tuberculosis and Changes following Anti-Tuberculosis Treatment.

PurposeInformation on the gut microbiome in patients with intestinal tuberculosis (ITB) and changes therein following anti-tuberculosis treatment (ATT) is lacking. We aimed to elucidate differences in stool microbiome between ITB patients and controls and to evaluate stool microbiome changes after ATT.Materials and MethodsEleven patients with probable ITB underwent ATT for 6 months, with stool samples collected at 0, 2, and 6 months. We performed next-generation sequencing of 16S rRNA genes in stool bacteria and compared the gut microbiome.ResultsInitially, the relative abundance of Verrucomicrobia was higher (5.0% vs. <1%) and that of Proteobacteria was lower (<1% vs. 6.6%) in ITB patients than in controls. Higher numbers of butyrate-producing bacteria (Blautia and Roseburia) were noted in ITB patients. The alpha-diversity of stool microbiome of ITB patients was lower than that in controls (p=0.045). There was a significant difference in beta-diversity between the groups (p=0.001). At 6 months, the proportion of Verrucomicrobia decreased to <1%, while the proportion of Proteobacteria remained at <1%.ConclusionThere were no significant differences in alpha- and beta-diversity in the stool microbiome at 0, 2, and 6 months after ATT. The stool microbiome composition of probable ITB patients was different from that of controls, and 6 months of ATT did not significantly affect it.

A combination of circulating microRNA-375-3p and chemokines CCL11, CXCL12, and G-CSF differentiate Crohn\u2019s disease and intestinal tuberculosis

Differentiation of Crohn’s disease (CD) from intestinal tuberculosis (ITB) is a big challenge to gastroenterologists because of their indistinguishable features and insensitive diagnostic tools. A non-invasive biomarker is urgently required to distinguish ITB/CD patients particularly in India, a TB endemic region, where CD frequency is increasing rapidly due to urbanization. Among the three differentially expressed miRNAs obtained from small RNA transcriptomic profiling of ileocaecal/terminal ileal tissue of ITB/CD patients (n = 3), only two down-regulated miRNAs, miR-31-5p, and miR-215-5p showed comparable data in qRT-PCR. Out of which, only miR-215-5p was detectable in the patient’s plasma, but there was no significant difference in expression between ITB/CD. On the other hand, miR-375-3p, the pulmonary TB specific marker was found in higher amount in the plasma of ITB patients than CD while reverse expression was observed in the ileocaecal/terminal ileal tissues of the same patients. Next, using Bioplex pro-human cytokine 48-plex screening panel, only three chemokines, Eotaxin-1/CCL11, SDF-1α/CXCL12, and G-CSF have noted significantly different levels in the serum of ITB/CD patients. ROC analysis has revealed that compared to a single molecule, a combination of miR-375-3p + Eotaxin-1/CCL11 + SDF-1α /CXCL12 + G-CSF showed a better AUC of 0.83, 95% CI (0.69–0.96) with 100% specificity and positive predictive value while sensitivity, negative predictive value, and accuracy were 56%, 69%, and 78% respectively in distinguishing ITB from CD. This study suggests that a combination of plasma markers shows better potential in differentiating ITB from CD than a single marker and this panel of markers may be used for clinical management of ITB/CD patients.

Value of Fecal Calprotectin Measurement During the Initial Period of Therapeutic Anti-Tubercular Trial.

Background/AimsThe diagnosis of intestinal tuberculosis (ITB) is often challenging. Therapeutic anti-tubercular trial (TATT) is sometimes used for the diagnosis of ITB. We aimed to evaluate the changing pattern of fecal calprotectin (FC) levels during TATT in patients with ITB. MethodsA retrospective review was performed on the data of 39 patients who underwent TATT between September 2015 and November 2018 in five university hospitals in Daegu, South Korea. The analysis was performed for 33 patients with serial FC measurement reports. ResultsThe mean age of the participants was 48.8 years. The final diagnosis of ITB was confirmed in 30 patients based on complete mucosal healing on follow-up colonoscopy performed after 2 months of TATT. Before starting TATT, the mean FC level of the ITB patients was 170.2 μg/g (range, 11.5-646.5). It dropped to 25.4 μg/g (range, 11.5-75.3) and then 23.3 μg/g (range, 11.5-172.2) after one and two months of TATT, respectively. The difference in mean FC before and one month after TATT was statistically significant (p<0.001), and FC levels decreased to below 100 μg/g in all patients after one month of TATT. ConclusionsAll ITB patients showed FC decline after only 1 month of TATT, and this finding correlated with complete mucosal healing in the follow-up colonoscopy after 2 months of TATT.

Development and validation of a new algorithm model for differential diagnosis between Crohn's disease and intestinal tuberculosis: a combination of laboratory, imaging and endoscopic characteristics

BackgroundSometimes in clinical practice, it is a great challenge to distinguish Crohn's disease (CD) and intestinal tuberculosis (ITB), we conducted this study to identify simple and useful algorithm for distinguishing them.MethodsWe retrospectively reviewed the medical history of the patients who were diagnosed as ITB or CD. We firstly identified ITB patients, and then the patients diagnosed with CD were matched by age, sex, and admission time in a 1:1 ratio. Patients who admitted between May 1, 2013 and April 30, 2019 were regarded as training cohort, and patients admitted between May 1, 2019 and May 1, 2020 were regarded as validation cohort. We used multivariate analysis to identify the potential variables, and then we used R package rpart to build the classification and regression tree (CART), and validated the newly developed model.ResultsIn total, the training cohort included 84 ITB and 84 CD patients, the validation cohort included 22 ITB and 22 CD patients. Multivariate analysis showed that, positive interferon-gamma release assays (IGRAs), ≥ 4 segments involved, longitudinal ulcer, circular ulcer, and aphthous ulcer were confirmed as independent discriminating factors. Using these parameters to build the CART model made an overall accuracy rate was 88.64%, with sensitivity, specificity, NPV, and PPV being 90.91%, 86.36%, 90.48% and 86.96%, respectively.ConclusionWe developed a simple and novel algorithm model covering laboratory, imaging, and endoscopy parameters with CART to differentiate ITB and CD with good accuracy. Positive IGRAs and circular ulcer were suggestive of ITB, while ≥ 4 segments involved, longitudinal ulcer, and aphthous ulcer were suggestive of CD.

Deep-learning system for real-time differentiation between Crohn's disease, intestinal Behçet's disease, and intestinal tuberculosis.

Pattern analysis of big data can provide a superior direction for the clinical differentiation of diseases with similar endoscopic findings. This study aimed to develop a deep-learning algorithm that performs differential diagnosis between intestinal Behçet's disease (BD), Crohn's disease (CD), and intestinal tuberculosis (ITB) using colonoscopy images. The typical pattern for each disease was defined as a typical image. We implemented a convolutional neural network (CNN) using Pytorch and visualized a deep-learning model through Gradient-weighted Class Activation Mapping. The performance of the algorithm was evaluated using the area under the receiver operating characteristic curve (AUROC). A total of 6617 colonoscopy images of 211 CD, 299 intestinal BD, and 217 ITB patients were used. The accuracy of the algorithm for discriminating the three diseases (all-images: 65.15% vs typical images: 72.01%, P=0.024) and discriminating between intestinal BD and CD (all-images: 78.15% vs typical images: 85.62%, P=0.010) was significantly different between all-images and typical images. The CNN clearly differentiated colonoscopy images of the diseases (AUROC from 0.7846 to 0.8586). Algorithmic prediction AUROC for typical images ranged from 0.8211 to 0.9360. This study found that a deep-learning model can discriminate between colonoscopy images of intestinal BD, CD, and ITB. In particular, the algorithm demonstrated superior discrimination ability for typical images. This approach presents a beneficial method for the differential diagnosis of the diseases.

Validation of models using basic parameters to differentiate intestinal tuberculosis from Crohn's disease: A multicenter study from Asia.

Data on external validation of models developed to distinguish Crohn's disease (CD) from intestinal tuberculosis (ITB) are limited. This study aimed to validate and compare models using clinical, endoscopic, and/or pathology findings to differentiate CD from ITB. Data from newly diagnosed ITB and CD patients were retrospectively collected from 5 centers located in Thailand or Hong Kong. The data was applied to Lee, et al., Makharia, et al., Jung, et al., and Limsrivilai, et al. model. Five hundred and thirty patients (383 CD, 147 ITB) with clinical and endoscopic data were included. The area under the receiver operating characteristic curve (AUROC) of Limsrivilai's clinical-endoscopy (CE) model was 0.853, which was comparable to the value of 0.862 in Jung's model (p = 0.52). Both models performed significantly better than Lee's endoscopy model (AUROC: 0.713, p<0.01). Pathology was available for review in 199 patients (116 CD, 83 ITB). When 3 modalities were combined, Limsrivilai's clinical-endoscopy-pathology (CEP) model performed significantly better (AUROC: 0.887) than Limsrivilai's CE model (AUROC: 0.824, p = 0.01), Jung's model (AUROC: 0.798, p = 0.005) and Makharia's model (AUROC: 0.637, p<0.01). In 83 ITB patients, the rate of misdiagnosis with CD when used the proposed cutoff values in each original study was 9.6% for Limsrivilai's CEP, 15.7% for Jung's, and 66.3% for Makharia's model. Scoring systems with more parameters and diagnostic modalities performed better; however, application to clinical practice is still limited owing to high rate of misdiagnosis of ITB as CD. Models integrating more modalities such as imaging and serological tests are needed.

PREVALENCE, DISTRIBUTION AND DETERMINANTS OF INTESTINAL TUBERCULOSIS IN ADULT INDOOR PATIENTS WITH ACUTE SMALL INTESTINAL OBSTRUCTION IN POPULATION OF PESHAWAR DIVISION, PAKISTAN

Background: Acute small intestinal obstruction (ASIO) is one of the commonest causes of emergency hospital admissions, morbidity and mortality. Intestinal tuberculosis (ITB) is common cause of ASIO in developing countries leading to significant morbidity and mortality. Our objectives were to determine prevalence, distribution and determinants of ITB in adult indoor patients with ASIO in population of Peshawar Division, Pakistan.Materials Methods: This cross-sectional study was conducted at Department of Surgery Peshawar Medical College, Peshawar, Pakistan from January 2019 to June 2020. The data was collected from its three affiliated hospitals; Mercy Teaching Hospital, Kuwait Teaching Hospital Prime Teaching Hospital, Peshawar. 207 ASIO subjects were selected from population at risk consecutively. Sex, age groups and presence of ITB were variables. Prevalence and distribution were described by count, percentage and confidence intervals for proportion for population. Hypotheses for distribution were tested by chi-square goodness of fit and of association by chi-square test of association.Results: Out of 207 patients with ASIO, 128 (61.84%) were men and 79 (38.16%) women, 87 (42.03%) were in age group 18-40 and 120 (57.97%) in 41-60 years. Out of 207 patients with ASIO, 41 (19.81%) had ITB, while 166 (80.19%) had no ITB. Out of 41 ITB patients, 25 (12.08%) were men and 16 (7.73%) women, 17 (8.21%) in age group 18-40 and 24 (11.60%) in 41-60 years. The prevalence of ITB was similar to expected (p=.5695). The distribution across sex (p=.00001) was different and across age groups (p=.12501) was similar to expected. Presence of ITB was not associated to sex (p=.8992) and age groups (p=.9347).Conclusion: Prevalence of intestinal TB in adult indoor acute small intestinal obstruction (ASIO) population of Peshawar Division, Pakistan was 19.81%. Prevalence was higher in men than women and higher in 41-60 years than 18-40 years age group population. Overall prevalence of intestinal TB was similar to expected. Observed distribution across sex was different and across age groups was similar to expected. Presence of intestinal TB was not associated to sex and age groups respectively.

Serial measurements of faecal calprotectin may discriminate intestinal tuberculosis and Crohn's disease in patients started on antitubercular therapy.

Response to antitubercular therapy (ATT) is often used to differentiate intestinal tuberculosis (ITB) from Crohn's disease. Role of non-invasive biomarkers to predict mucosal response to ATT is unclear. A prospective study to compare faecal calprotectin and serum C-reactive protein (CRP) levels at diagnosis, 2 and 6 months of ATT in patients with suspected ITB started on ATT was done. The patients were eventually divided into two groups: ITB or alternative diagnosis (OTH). Decline of calprotectin and CRP levels was used to compute area under the receiver operating characteristic (AUROC) to predict mucosal healing at 2 months. Thirty-seven patients (mean age: 34.95 ± 16.35 years, 23 males) were included and 28 (75.67%) were diagnosed as ITB while nine (24.32%) had alternative diagnosis (OTH). The median faecal calprotectin values of ITB and OTH groups at baseline, 2 months and 6 months were 216 and 282 µg/g (P = 0.466), 43 and 216 µg/g (P = 0.003), and 26 and 213 µg/g (P < 0.001), respectively. The median CRP values at baseline, 2 months and 6 months were 18 and 30 mg/L (P = 0.767), 4.7 and 15 mg/L (P = 0.025), and 3 and 10.85 mg/L (P = 0.068), respectively. The AUROC of percent decline in faecal calprotectin and serum CRP at 2 months for mucosal healing were 0.8287 [95% confidence inteval (CI) 0.6472-1] and 0.6018 (95% CI 0.4079-0.7957), respectively. Faecal calprotectin can help in assessing response to therapy in suspected ITB patients started on empirical ATT.

Prospective validation of CD4+CD25+FOXP3+ T-regulatory cells as an immunological marker to differentiate intestinal tuberculosis from Crohn’s disease

Background/AimsCrohn’s disease (CD) and intestinal tuberculosis (ITB) remain “difficult-to-differentiate” diseases. We have previously documented peripheral blood frequency of CD4+ CD25+ FOXP3+ T-regulatory cells (Treg) as a biomarker to differentiate CD and ITB. We tried to validate these results in a larger cohort of CD and ITB patients.MethodsSeventy treatment naïve patients of CD (n = 23) and ITB (n = 47) (diagnosed by standard criteria) were recruited prospectively from October 2016 to May 2017. Patients with history of antitubercular therapy in the past were excluded. The frequency of Treg cells in peripheral blood was determined by flow cytometry, and compared between CD and ITB patients.ResultsSimilar to our previous study, frequency of Treg cells in peripheral blood was significantly increased in ITB as compared to CD patients (40.9 [interquartile range, 33–50] vs. 24.9 [interquartile range, 14.4–29.6], P<0.001). Further, the receiver operating characteristics curve also showed good diagnostic accuracy with an area under the curve (AUC) of 0.77 (95% confidence interval, 0.65–0.89) and a FOXP3+ cutoff value of > 31.3% had a sensitivity and specificity of 83% and 82.6% respectively, to differentiate ITB from CD. Even for the indeterminate cases (n = 33), Treg cell frequency had similar diagnostic accuracy with an AUC of 0.85 (95% confidence interval, 0.68–0.95) and a cutoff of 32.37% had sensitivity and specificity of 87% and 95% respectively, to differentiate ITB from CD.ConclusionsThe current findings validate that the increased frequency of CD4+ CD25+ FOXP3+ Treg in the peripheral blood can be used as a biomarker with high diagnostic accuracy to differentiate ITB from CD.

Levels of TB-IGRA may help to differentiate between intestinal tuberculosis and Crohn's disease in patients with positive results.

Aim:The aim of this study was to investigate the significance of positive tuberculosis interferon gamma release assay (TB-IGRA) in the differential diagnosis of intestinal tuberculosis (ITB) and Crohn’s disease (CD) patients, and to find a suitable threshold to help distinguishing CD from tuberculosis (TB), so as to provide better recommendations for clinical treatment.Methods:A retrospective study was performed including 484 patients who underwent TB-IGRA testing for suspected CD or ITB treated in the Shanghai Tenth People’s Hospital of Tongji University between January 2015 and May 2018. According to the diagnostic criteria, 307 patients, including 272 CD and 35 ITB patients, were recruited for the final analysis. We comprehensively and systematically collected their clinical manifestations, and analyzed the influence of TB-IGRA values referring to diagnosis criteria, and the possible causes of false positives. The receiver operator characteristic (ROC) curve and the cut-off value were applied to distinguish between ITB and CD patients.Results:Of the 56 patients with suspected CD enrolled, 23 were finally diagnosed with CD and 33 with ITB. In patients with TB-IGRA ⩾ 100 pg/ml, 4 cases were CD and 29 cases were ITB, while 19 cases were CD and 4 cases were ITB in patients with TB-IGRA < 100 pg/ml (p < 0.05). TB-IGRA ⩾ 100 pg/ml indicated a high possibility of TB infection, with a sensitivity of 88% and a specificity of 74%. Three out of the four CD patients with TB-IGRA ⩾ 100 pg/ml had a history of tuberculosis, while only 1 of the 19 CD patients with TB-IGRA < 100 pg/ml had a history of tuberculosis (p < 0.05). The average duration of ITB was 7 months, and that of CD was 46.8 months, thus a significant difference (p < 0.05) was observed. Perianal lesions such as anal fistula or abscess were found in all CD patients. Among ITB patients, 8 out of 15 patients with TB-IGRA ⩾ 400 pg/ml experienced weight loss, while only 1 out of 18 patients with TB-IGRA < 400 pg/ml underwent weight loss (p < 0.05).Conclusion:Patients with CD have longer duration of disease, and perianal lesions are more common in CD. ITB patients with TB-IGRA ⩾ 400 pg/ml experience weight loss more readily, which indicates that TB-IGRA value may be correlated positively with the severity of ITB. In patients with CD and ITB, TB-IGRA = 100 pg/ml may be a cut-off value of TB-IGRA. For patients with TB-IGRA ⩾ 100 pg/ml, it is recommended to use diagnostic anti-TB treatment first. Comprehensive analysis and judgment are required for patients with TB-IGRA from 14 pg/ml to 99 pg/ml. TB-IGRA false positivity may occur in patients with a history of TB infection.

Ten Cases of Intestinal Tuberculosis Which Were Initially Misdiagnosed as Inflammatory Bowel Disease.

Objective Intestinal tuberculosis (ITB) and inflammatory bowel disease (IBD) frequently present with similar clinical, endoscopic and pathological features, therefore it is difficult to differentiate between them. The aim of this study was to elucidate the diagnostic delay and prognosis of ITB cases, initially misdiagnosed as IBD. Methods ITB cases were selected from the hospitalized patient list between April 2004 and March 2017 in a tuberculosis center in Japan. We retrospectively evaluated the initial diagnosis, clinical characteristics, endoscopic and pathological findings, bacterial examinations, treatment and prognosis. Results Among 66 ITB patients, ten patients were initially misdiagnosed as IBD. Seven patients were male and the median age was 60.5 years (23-74 years). After the diagnosis of IBD, all the patients were treated with mesalazine, in addition to corticosteroids in two patients and sequential azathioprine and infliximab in one. The median duration of diagnostic delay was 5.5 months (range 0.5-17 months). Eight patients had active pulmonary tuberculosis at the diagnosis of ITB. Acid-fast bacilli were confirmed in four of seven patients by reevaluation of the pathological specimens at the IBD diagnosis. Two patients needed intestinal resection and one with erroneous corticosteroid use for IBD died due to respiratory failure in spite of receiving appropriate treatment for tuberculosis. Conclusion ITB patients were frequently misdiagnosed and treated as IBD, thus resulting in a poor clinical outcome even after finally making a correct diagnosis and administering appropriate treatment. On diagnosis of IBD and/or treatment failure, chest radiograph and acid-fast bacilli of the pathological specimens should be carefully evaluated in order to rule out tuberculosis.

Intestinal tuberculosis: clinico-pathological profile and the importance of a high degree of suspicion.

Intestinal tuberculosis (ITB) remains prevalent and a big health hazard in China. The aim of this study was to retrospectively analyse its clinico-pathological features. Retrospective study of 85 consecutive ITB patients in two tertiary hospitals in East China. Relevant clinical, laboratory examination, radiological, endoscopic and histopathological features of ITB were recorded. The mean age was 37.3±16.0years; 56 patients (65.9%) were male. 67.1% had ITB secondary to pulmonary tuberculosis. The overall median length of hospital stay was 28days and was significantly longer in patients with intestinal complications (P=0.003) and malnutrition (P=0.042). Abdominal pain (88.2%) and weight loss (75.3%) were the commonest symptoms. The positive rate of the purified protein derivative (PPD) test was 88.2%; of the T-spot, 85.7%. Histopathology revealed caseating granuloma in 70.6% and caseating necrosis in 24.7% of patients. The most commonly affected sites were the ileocecal valve (56, 65.9%), terminal ileum (40, 47.1%) and caecum (33, 38.8%). Only 17 (20%) patients were initially diagnosed as ITB, the other 68 patients were misdiagnosed. Six patients with caecum tuberculosis were misdiagnosed as appendicitis, four of whom had improper surgical procedures followed by post-operative intestinal fistulas; two died due to MODS. Diagnosis of ITB is often misdirected and delayed, which may lead to inappropriate treatment and high mortality. High diagnostic suspicion is necessary for patients with unexplained abdominal complaints. Diagnosis is not easy but could benefit coexisting pulmonary tuberculosis, T-spot, CT imaging, colonoscopy, pathological features, acid-fast bacilli and response to anti-tuberculosis therapy (ATT).

Tubercular Intestinal Strictures Show a Poor Response to Anti-Tuberculous Therapy.

The literature on resolution of intestinal strictures in patients with intestinal tuberculosis (ITB) after anti-tuberculous therapy (ATT) is sparse and ambivalent. We aimed to assess the frequency of stricture resolution after ATT and its predictors. This ambispective cohort study included consecutive ITB patients with strictures who received ATT for ≥6months and were on regular follow-up between January 2004 and December 2015. Resolution of stricture was assessed at the end of ATT by endoscopy/radiology. Of 286 patients, 128 had strictures, and 106 were finally included (63 males, median age 35years). The stricture location was distal ileum/ileocecal in 52 (49.1%), colon in 37 (34.9%), ileocolonic in 4 (3.8%), proximal small bowel in 10 (9.4%), and gastroduodenal in 4 (3.8%) patients. Although all patients demonstrated mucosal healing (indicating resolution of active infection), stricture resolution occurred only in 25/106 (23.6%) patients. Symptoms pertaining to stricture (pain abdomen/recurrent SAIO) were present in 104/106 (98%) patients, and after a median of 6 (6-9) months of ATT, these symptoms resolved only in half, 88% (22/25) in patients with stricture resolution and 38% (30/79) in patients with persistent strictures. Colonic strictures had the least resolution (5.4%) followed by proximal small intestinal (20%) and distal ileal/ileocecal (36.5%). Although not statistically significant, stricture resolution was less frequent in patients with multiple strictures, longer strictures (>3cm), and strictures in which scope was not negotiable prior to ATT. Only one-fourth of ITB patients with strictures show resolution of stricture following ATT. The resolution of strictures is dependent on disease location, and majority of them exhibit symptoms pertaining to stricture even after ATT.